We operate BSL-2 R&D and GMP manufacturing facilities. The GMP facility is equipped to run up to 200 L mammalian cell line-based processes and is fully licensed to manufacture viral vectors. In our facility, we also manufacture GMP-grade master and working cell banks and master and working virus seeds. Overseeing quality is a Qualified Person (QP), Quality Control (QC) department and Quality Assurance (QA) department.
We appoint a dedicated project manager to each project, whether pre-clinical or clinical manufacturing. The project manager is usually already familiar with the project, having been involved in the quotation writing process. The project manager acts as the “eyes and ears” of the customer, ensuring that the organization delivers on promises. These are defined in deliverables so that overall milestones are met in time and according to budget. Hereto, the project manager is tasked with building the project team. This cross-functional team comprises all contributing functional departments required for the execution of the project.
The project manager serves as the central point of contact for the customer in all project-related matters. Therefore, frequent meetings between the customer and the project manager are scheduled during the project. During these meetings, the project manager informs the customer on progress, deliverables met, challenges, delays, and hurdles and, should it be required, proposes potential solutions to mitigate any deviations from the set timelines.
Batavia Biosciences’ Viral vector manufacturing track record
We have performed over 50 viral vector projects for large pharmaceutical companies, biotechnology companies and non-profit organizations with superb customer satisfaction.
Pre-Clinical Manufacturing of Viral Vectors
Your pre-clinical research is only valuable if your data can be reproduced. This requires the use of high-quality and well-characterized research materials. Our capabilities and experience qualify us to be your research partner and manufacture your viral vector products.
Generating a viral vector batch is initiated by molecular cloning of the gene of interest into the vector backbone. This can be achieved by traditional cloning methods or by DNA synthesis. All our plasmid stocks are quality controlled by restriction enzyme analyses, PCR assays, and DNA sequencing. Plasmids are amplified and then stored at -20°C. Depending on the vector to be manufactured, up to 4 plasmids are mixed and transfected into appropriate cell lines. We have experience with a variety of DNA transfection protocols, including the use of electroporation-, chemical- or lipid-based protocols.
Cell lines for viral vector production
We have developed optimized transfection protocols for important viral vector support cell lines, including parental and modified Vero (measles and VSV vector) and HEK293 (AAV, adenoviral and lentiviral vector) cell lines. Research production runs can range from small-scale vector generation, for instance, to support library screening purposes, to large-scale production in cell factories or shake flasks to support pivotal in vivo studies. Upon harvesting of vector material, or passaging in case packing cell lines are used, vectors are purified using research protocols. These protocols typically involve centrifugation-based methods. In addition, buffers and protocols for the formulation and storage of those vectors are available.
All research materials are delivered with a certificate of analysis listing characteristics such as yield, purity, integrity and identity. Certificates of analyses can further include mycoplasma and sterility testing results in case materials are to be used for in vivo studies. Owing to the vast experience of our R&D team, the company is primed to deliver high-quality research materials supporting pre-clinical studies.
Small-scale viral vector production
For small-scale productions, we offer our SCOUT® technology. This platform enables rapid process optimization by integrating scaled-down, high-throughput cell culture systems with high-throughput purification and analytical capabilities.
Large-scale viral vector production
For large-scale productions, we offer MaxCyte cell transfection technology in combination with our in-house animal component-free medium or customer-developed medium, using either batch, fed-batch, perfusion or customer-developed processes.
Viral vector purification and analysis
The different upstream scales are matched with appropriately scaled downstream equipment for clarification, chromatography and filtration. For the purification of viral vectors, we offer (but are not limited to) clarification by depth filtration with various filters. This includes filters that combine particle purification and impurity removal. For product analysis, we offer various product-specific assays and assay development services, such as TCID50, plaque and neutralization assays, ELISA, (q)PCR and various chromatography methods.
Clinical Manufacturing of Viral Vectors
Equipment needed for Clinical Manufacturing of Viral Vectors
It is ingrained in our company culture always to suggest manufacturing equipment for clinical manufacturing that is in line with the equipment for commercial manufacturing. It is therefore deemed crucial first to understand commercial manufacturing scale and perceived process, as this will ensure a smooth transition of the candidate product from clinical trials to a commercial manufacturing setting. Therefore, we accommodate a variety of clinical manufacturing platforms, including a stirred tank 200 L bioreactor, single-use bioreactors, spinner flasks, shake flasks, roller bottles and cell factories to produce drug substances.
Quality system for Clinical Manufacturing of Viral Vectors
All our systems and procedures are developed and maintained to ensure compliance with applicable FDA and EMA regulatory requirements and standards. Our Quality Team oversees the entire production process, from the validation of equipment to the approval of the documents required to release your product. Overall Quality Review is performed during quarterly meetings with executive management, focusing on adhering to the auditing scheme, critical and significant observations (if applicable), numbers of available quality incident reports, changes and CAPAs closure within due date and trends.
We have successfully built a system where the team of experts developing the processes in an R&D environment also performs the clinical manufacturing in GMP. This approach has proven to eliminate time-consuming and error-prone technology transfer processes. In addition, our dedicated team of experts is also closely involved in transferring the manufacturing process to the customer’s late-stage or commercial manufacturer.
Facilities for clinical manufacturing
We operate grade B and C clean room facilities. The facilities have dedicated upstream and downstream suites with various manufacturing platforms. In addition, GMP materials warehousing and storage areas support the facilities. Storage is available at room temperature, 5°C, -20°C, -80°C and in liquid nitrogen, with dedicated space for drug substance and drug product stability testing. Regulatory authorities and customers regularly audit our GMP facilities. We are proud to host more than 8 audits each year and have passed every audit with flying colours, as none of the audits has demonstrated critical observations.
Product Release and Regulatory Support
We offer expert manufacturing and regulatory support in translating processes into regulatory dossiers. Our Quality Management System covers three tiers of quality: Research with GRP WHO guidelines as a basis, Process Development based on GRP and ICH Q8/9/10 and Assay Development to ICH Q2, and finally, GMP based on EU GMP and ICH Q10.
Manufacturing license for Viral Vectors
The Dutch authorities license Batavia Biosciences for the production of biopharmaceuticals (license number 5468 F) according to EU GMP regulations. This license covers the release of biopharmaceuticals in three categories: biotechnology products, gene therapy products and immunological products. Batavia Biosciences’ QA and QC departments are closely involved in the release of products.
Batch release by in-house QP
The operators of production and QC are responsible for accurately and faithfully recording all data generated during the manufacturing and testing of components and products. The head of the production and QC review the data generated, while QA audits the documentation and compiles the batch dossier. Our in-house QP reviews all batch-related documents and approves the Certificate of Analysis and the Certificate of Compliance. She registers the release of the batch in the Batch Manufacturing Log. The customer may audit the batch dossier on-site or review copies.
We have successfully supported many INDs and IMPDs covering diverse biopharmaceuticals and novel and bio-similar products. Our experienced staff offers their support in preparing and reviewing the CMC section of the IND or IMPD. They also provide support in meetings with the regulatory authorities. Even though we support IND and IMPD documentation, we do not file the IND or IMPD nor perform pre-clinical safety and clinical studies.